Reproduction via
cis-binary mechanisms appears to have evolved fairly early in the evolution of
complex organisms, and a system committed to prior to evolution of humans.
While the evolution of a chromosomal-specific approach has been a successful
strategy for survival of a large variety of species including humans, the
fidelity of sex determination leading to 100% cis-binary outcomes is not
achieved in many species, with evidence for homosexual or bisexual behaviour
evident in more than 1500 species. Thus, such outcomes indicates that sex
determination is a multi-step process and not a single event, and as such,
could lead to the appearance of variants during the process which developed
much earlier than humans. Variants could arise either due to intrinsic
variation in the steps of determination, or also be influenced by environmental
factors of a biological or psychological nature. In contrast to homosexual
variants which do not require interventions such as hormone therapy or surgery,
expression of gender dysphoria, is more based in psychology, but also has
biological underpinnings and can be influenced by such hormonal interventions
and surgery. While the numbers of those with gender dysphoria is small (~0.6% -
1.0% of population), the attention given to this issue raises the possibility
of biological and psychological environmental factors impacting the emergence
of some of those expressing gender dysphoria. Furthermore, transitioning from
male-to-female or female-to-male can have consequences regarding disease risks
latter in life, including the appearance of autoimmune diseases. This review
will attempt to review some of the evidence regarding sex determination,
discuss why the system has potentially not been improved upon during evolution,
how a potential role for sex chromosome function on neurodevelopment may be
central to variation in humans, and how commitment to the current strategy is
likely integrated into other sex-related events such as puberty, pregnancy, and
menopause to ensure species survival. It will also discuss how variants in sex
determination could contribute to sex differences in disease risk and how epigenetic
modifications could play a role in such risk.
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